Study to Evaluate the Effect of Dose and Duration of Treatment of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) on Safety, Tolerability, and Potential Outcomes in Adult Patients With ABPA
The goal of this clinical trial is to learn about PUR1900 as an inhaled, antifungal therapeutic for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma. The main questions it aims to answer are: 1. Is PUR1900 safe and well tolerated in adults with asthma and ABPA? 2. Is there an effect of daily administration of PUR1900 on potential outcome measures in adults with asthma and ABPA? 3. Is there fungal resistance to A. fumigatus? This study includes a 28-day screening period, a 112-day (16-week) treatment period, and a 56-day (8 week) observation period. Participants will take either 40mg of PUR1900, 20 mg of PUR1900 or Placebo for 112 days and complete an eDairy, answer questions about their asthma and complete peak respiratory flow measurements at home. They will come to the clinic approximate once a month during the treatment period and complete study assessments. At the end of the observation period participants will complete one more clinic visit. Participants who complete this study may be given the opportunity to continue on study drug in an open label extension study.
• Is a male or female, ≥18 years old at the time of signing the informed consent.
• BMI of ≥18.0 and \<40.0 kg/m2 at screening.
• Has a diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update
• Has a confirmed diagnosis of ABPA, based on the modified International Society for human and Animal Mycology (ISHAM) ABPA working group 2013 and 2021 criteria including a history of or documentation at screening of serum IgE ≥ 500 IU/mL and A. fumigatus-specific IgE\>0.35KUA/L, or above normal IgE antibody to A. fumigatus, or a positive immediate skin test and at least 2 of the 3 following supportive criteria: eosinophil count \>500 cells/µL; A. fumigatus-specific IgG \>27 mgA/L or presence of precipitating (or above normal immunoglobulin G \[IgG\]) antibody to A. fumigatus; consistent radiographic opacities or bronchiectasis on chest CT.
• Is currently considered to be in one of the following stages of ABPA: Stage 2 (Response), Stage 4 (Remission), Stage 5a (Treatment-dependent ABPA), or Stage 5b (Glucocorticoid-dependent asthma).
• At least 1 exacerbation requiring a systemic glucocorticosteroid(s) in the 12 months prior to Screening. For patients on a biologic agent, at least one exacerbation requiring a systemic glucocorticosteroid(s) must have occurred at least 3 months after the initiation of the biologic agent.
• Has a serum IgE ≥500 IU/mL at screening.
• Has a documented stable asthma medication regimen during the 28 days prior to the first dose of study drug ; applicable asthma medications can include but are not limited to the following: inhaled short-acting beta agonist (SABA), inhaled long-acting beta agonist (LABA), and leukotriene receptor antagonist (LTRA) use and inhaled and/or oral glucocorticosteroids. SABA use during this period should be mostly within a stable range (e.g., 2 puffs 2 to 4 times a day) and should not exceed 8 puffs a day on 2 out of 3 consecutive days.
• Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 ≥50% of predicted normal for age, sex, race, and height at a screening visit.
• Can demonstrate the correct inhalation technique and achieve a minimum inspiratory flow rate of 45 L/min for the use of the delivery device at screening and before dosing on Day 1.
• Is willing and able to comply with all study procedures and assessments, including scheduled visits, drug dosing plan, study procedures, laboratory tests, and study restrictions.
• Subjects who are sexually active, male subjects able to father a child, and female subjects of childbearing potential must agree to follow contraception requirements.